Results: The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, –0.20 to 2.84; P=.088) on the IDS-SR30 and 0.97 points (95% CI, –0.012 to 1.95; P=.053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P=.035). For patients without comorbid anxiety disorders (n=204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR30 (95% CI, 0.89 to 5.45; P=.007) and 1.93 points (95% CI, 0.50 to 3.36; P=.008) on the MADRS.

Conclusions: In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders.